Plants of the genus Sceletium are known to contain an alkaloid content including indole alkaloids such as mesembrenol, mesembranol, mesembrine and mesembranone, the chemical formulae of which are described in U.S. Pat. No. 6,288,104. Plants of the genus Sceletium are known to vary widely in terms of the total alkaloid content, as well as the chemistry and relative concentrations of individual Sceletium alkaloids (Gericke, N. and A. M. Viljoen. Sceletium—a review update. Journal of Ethnopharmacology 119 (2008) 653-663). It is reported that mesembrine is the main active ingredient in Mesembryanthemum tortuosum (van Wyk, B.-E., B. van Oudtshoorn and N. Gericke 2009. Medicinal Plants of South Africa, 2nd Edition, Briza, Pretoria). (Mesembryanthemum tortuosum is a botanical synonym for Sceletium tortuosum). It is reported in U.S. Pat. No. 6,288,104 that mesembrine is virtually the only alkaloid present in the leaves of the species Sceletium tortuosum. U.S. Pat. No. 6,288,104 describes mesembrine, mesembrenol and mesembranone as having potent 5-HT uptake inhibitory activity and as being useful in treating mental health conditions such as mild to moderate depression. Mesembrine hydrochloride has previously been reported to be a weak PDE4 inhibitor (Napoletano, M. et al. 2001. Mesembrine is an inhibitor of PDE4 that follows the structure-activity relationship of rolipram. Chemistry Preprint Archive, Volume 2001, Issue 3, March 2001, Pages 303-308).
It is generally believed that plants of the genus Sceletium, and extracts thereof, should preferably contain high concentrations of mesembrine to contribute substantially to the known biological activity thereof. For bioactive plant extracts intended for human or animal consumption it is desirable to have a reproducible and stable phytochemical profile for the plant material, and for any extract or pharmaceutical composition produced from that plant material. However, mesembrine has been reported to be unstable under a variety of conditions that can occur while harvesting, drying, and extracting the raw material, as well as during storage and formulation of the extract. Mesembrine has been shown to be unstable under conditions of fermentation, exposure to light, exposure to heat, and in an aqueous medium (Patnala, S. and Kanfer, I. Investigations of the phytochemical content of Sceletium tortuosum following the preparation of “Kougoed” by fermentation of plant material. J Ethnopharmacol. 2009 Jan. 12; 121(1):86-91).
The applicant has found that it is able to produce a novel composition which may be formulated as a pharmaceutical composition or a dietary supplement, which includes as an active ingredient an extract of a plant of the family Mesembryanthemaceae with mesembrenol and mesembrenone as the two major alkaloids present and having low or trace amounts of mesembrine and a selected minimum amount of mesembranol. The problems associated with stability are alleviated and surprisingly, notwithstanding the low mesembrine content, compositions in accordance with the invention, exhibit potent PDE-4 inhibition properties and retain potent serotonin uptake inhibition properties.